Dataset Information

Association between genetic variation of complement C3 and the susceptibility to advanced age-related macular degeneration: a meta-analysis.

ABSTRACT:

Background

The purpose of this study is to discuss whether genetic variants (rs2230199, rs1047286, rs2230205, and rs2250656) in the C3 gene account for a significant risk of advanced AMD.

Methods

We performed a meta-analysis using electronic databases to search relevant articles. A total of 40 case-control studies from 38 available articles (20,673 cases and 20,025 controls) were included in our study.

Results

In our meta-analysis, the pooled results showed that the carriage of G allele for rs2230199 and the T allele for rs1047286 had a tendency to the risk of advanced AMD (OR = 1.49, 95% CI = 1.39-1.59, P < 0.001; OR = 1.45, 95% CI = 1.37-1.54, P < 0.001). Moreover, in the subgroup analysis based on ethnicity, rs2230199 and rs1047286 polymorphisms were more likely to be a predictor of response for Caucasian region (OR = 1.48, 95% CI = 1.38-1.59, P < 0.001; OR = 1.45, 95% CI = 1.37-1.54, P < 0.001). Besides, pooled results suggested that the G allele of rs2230199 could confer susceptibility to advanced AMD in Middle East (OR = 1.62, 95% CI = 1.33-1.97, P < 0.001).

Conclusion

In our meta-analysis, C3 genetic polymorphisms unveiled a positive effect on the risk of advanced AMD, especially in Caucasians. Furthermore, numerous well-designed studies with large sample-size are required to validate this conclusion.

SUBMITTER: Zhang J

PROVIDER: S-EPMC6199710 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Publications

Association between genetic variation of complement C3 and the susceptibility to advanced age-related macular degeneration: a meta-analysis.

Zhang Jun J Li Shuang S Hu Shuqiong S Yu Jiguo J Xiang Yi Y

BMC ophthalmology 20181023 1

<h4>Background</h4>The purpose of this study is to discuss whether genetic variants (rs2230199, rs1047286, rs2230205, and rs2250656) in the C3 gene account for a significant risk of advanced AMD.<h4>Methods</h4>We performed a meta-analysis using electronic databases to search relevant articles. A total of 40 case-control studies from 38 available articles (20,673 cases and 20,025 controls) were included in our study.<h4>Results</h4>In our meta-analysis, the pooled results showed that the carriag ...[more]

PMID: 30352574

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Project description:PurposeTo evaluate associations between rare dysfunctional complement factor I (CFI) genetic variant status and progression to advanced age-related macular degeneration (AAMD), geographic atrophy (GA), and neovascular disease (NV).DesignProspective, longitudinal study.ParticipantsPatients aged 55 to 80 years at baseline identifying as White with non-AAMD in 1 or both eyes at baseline were included. Follow-up grades were assigned as early, intermediate, or AAMD (GA or NV). CFI variants were categorized using genotyping and sequencing platforms.MethodsAnalyses were performed using the Seddon Longitudinal Cohort Study (N = 2116 subjects, 3901 eyes, and mean follow-up of 8.3 years) and the Age-Related Eye Disease Study (N = 2837 subjects, 5200 eyes, and mean follow-up of 9.2 years). CFI rare variants associated with low serum factor I (FI) protein levels and decreased FI function (type 1), other AMD genetic variants, and demographic, behavioral, and ocular factors were evaluated. Generalized estimating equations methods were used to assess the association between CFI rare variants and progression, independent of other genetic variants and covariates.Main outcome measuresProgression to AAMD, GA, or NV.ResultsIn the prospective cohort of 4953 subjects (9101 eyes with non-AAMD at baseline), 1% were type 1 rare CFI carriers. Over 12 years, progression to AAMD was 44% for carriers and 20% for noncarriers (P < 0.001), 30% of carriers versus 10% of noncarriers progressed to GA (P < 0.001), and 18% of carriers compared with 11% of noncarriers progressed to NV (P = 0.049). CFI carriers were more likely to have a family history of AMD (P for trend = 0.035) and a higher baseline AMD grade (P < 0.001). After adjusting for all covariates, CFI carrier status was associated with progression to GA (odds ratio [OR] = 1.91; 95% confidence interval [CI] = 1.03, 3.52) but not NV (OR = 0.96). Higher body mass index was associated with progression among CFI carriers (body mass index ≥ 25 vs. < 25; OR = 5.8; 95% CI 1.5, 22.3) but not for noncarriers (OR = 1.1; 95% CI = 0.9, 1.3), with P_interaction = 0.011.ConclusionsResults suggest that carriers of rare dysfunctional type 1 CFI variants are at higher risk for progression to AAMD with GA.Financial disclosuresProprietary or commercial disclosure may be found after the references.

Project description:BackgroundGiven the relatively high prevalence of age-related macular degeneration (AMD) and the increased incidence of AMD as populations age, the results of trials of novel treatments are awaited with much anticipation. The complement cascade describes a series of proteolytic reactions occurring throughout the body that generate proteins with a variety of roles including the initiation and promotion of immune reactions against foreign materials or micro-organisms. The complement cascade is normally tightly regulated, but much evidence implicates complement overactivity in AMD and so it is a logical therapeutic target in the treatment of AMD.ObjectivesTo assess the effects and safety of complement inhibitors in the prevention or treatment of advanced AMD.Search methodsWe searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 11), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2013), EMBASE (January 1980 to November 2013), Allied and Complementary Medicine Database (AMED) (January 1985 to November 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to November 2013), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), Web of Science Conference Proceedings Citation Index - Science (CPCI-S) (January 1990 to November 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 21 November 2013. We also performed handsearching of proceedings, from 2012 onwards, of meetings and conferences of specific professional organisations.Selection criteriaWe planned to include randomised controlled trials (RCTs) with parallel treatment groups which investigated either the prevention or treatment of advanced AMD by inhibition of the complement cascade.Data collection and analysisTwo authors (MW and GMcK) independently evaluated all the titles and abstracts resulting from the searches. We contacted companies running clinical trials which had not yet reported results to request information. Since no trials met our inclusion criteria, we undertook no assessment of quality or meta-analysis.Main resultsWe identified and screened 317 references but there were no published RCTs that met the inclusion criteria. We identified two ongoing studies: one phase I study and one phase II study.Authors' conclusionsThere is insufficient information at present to generate evidence-based recommendations on the potential safety and efficacy of complement inhibitors for prevention or treatment of AMD. However we anticipate the results of ongoing trials.

Dataset Information

Association between genetic variation of complement C3 and the susceptibility to advanced age-related macular degeneration: a meta-analysis.

Background

Methods

Results

Conclusion

Publications

Association between genetic variation of complement C3 and the susceptibility to advanced age-related macular degeneration: a meta-analysis.

Similar Datasets

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